Burden of diseases due to high systolic blood pressure in the Middle East and North Africa region from 1990 to 2019

High systolic blood pressure (HSBP) is associated with several metabolic and non-metabolic disorders. This research aimed to document the deaths and disability-adjusted life-years (DALYs) attributable to HSBP in the Middle East and North Africa (MENA) region between 1990 and 2019, by age, sex, underlying cause and socio-demographic index (SDI). We used the methodological framework and data drawn from the Global Burden of Disease study 2019 to identify the burden of diseases attributable to HSBP, from 1990 to 2019, in the MENA region. The estimates reported were presented as counts, population-attributable fractions, and age-standardised rates (per 100,000), along with 95% uncertainty intervals. In 2019, 803.6 thousand (687.1 to 923.8) deaths were attributed to HSBP in MENA, which accounted for 25.9% (22.9–28.6%) of all deaths. The number of regional DALYs caused by HSBP in 2019 was 19.0 million (16.3–21.9 million), which accounted for 11.6% (10.1–13.3%) of all DALYs, and was 23.4% (15.9–31.5%) lower than in 1990. The highest age-standardised DALY rate for 2019 was observed in Afghanistan, with the lowest in Kuwait. Additionally, the DALY rate in MENA rose with age for both sexs. Furthermore, a negative linear relationship was found between SDI and the age-standardised DALY rates. The region has a substantial HSBP-related burden. Policymakers and healthcare professionals should prioritize interventions that effectively promote the early detection of HSBP, access to quality healthcare, and lifestyle modifications to mitigate the HSBP burden in the MENA countries.


Case Definitions and data sources
Continuous systolic blood pressure measurements (in mmHg) were used as the basis for evaluating hypertension 11 .The mean systolic blood pressure was derived from two main sources: (1) a systematic literature review that was conducted during the GBD 2015 study, and (2) data obtained from household surveys and related reports 11 .The GBD 2019 study utilised a vast collection of information and in the systematic literature review, only population-based studies that measured SBP using a sphygmomanometer were included.
Research that included non-representative populations, lacked sufficient methodological detail, or reported implausibly high or low SBP levels, based on expert judgement and data from similar countries, were excluded 11 .Whenever available, individual level blood pressure data were obtained using microdata derived from surveys.The data points were combined for different demographic groups to calculate average estimates within the GBD 5-year age-sex categories 11 .Where microdata was not available, data from surveys and literature sources were utilized, along with their associated measures of uncertainty (i.e., standard error, uncertainty interval, standard deviation, and sample size).However, these sources often focused solely on the prevalence of hypertension within the studied population, omitting details about the level of hypertension 11 .For the modeling of SBP, most of these sources were not utilized, except for the data acquired from the Behavioral Risk Factors Surveillance System (BRFSS), a self-reported survey that was undertaken via the telephone in the United States of America.The reason for this exception is that the BRFSS survey is structured similarly to the National Health and Nutrition Examination Survey (NHANES), which includes a sample that is representative of the population 11 .

Modeling strategy
The Institute for Health Metrics and Evaluation (IHME) employed spatiotemporal Gaussian process regression (ST-GPR) to predict the average systolic blood pressure for each country and subnational location, sex, and 5-year age categories (beginning at 25 years old), covering the years 1980 to 2019.The selection of covariates was conducted in two steps.Firstly, a set of variables with causal links to SBP was compiled.These variables were identified based on significant associations being found in reputable prospective cohort studies that were published in the scientific literature.Secondly, the predictive validity of all combinations of covariates within the linear model was assessed using the previously selected covariates as a foundation 11 .This process was conducted separately for each sex.The standard deviation of systolic blood pressure was then modelled for the different country and subnational populations, the researchers considered factors such as sex and 5-year age groups, beginning at 25 years old.The estimations were derived from the standard deviations of the person-level data, which was supplemented with information from tabulated data sources 11 .Moreover, a blood pressure adjustment was applied to prevent overestimation caused by measurement error, in addition to diurnal, seasonal, or biological variations 11 .

Relative risk
IHME estimated the Theoretical Minimum-Risk Exposure Level (TMREL) for SBP, which represents the level of exposure that reduces the possibility of experiencing any HSBP-related diseases to as low as possible.According to a synthesis of prospective cohort studies, the estimated TMREL of SBP falls within the range of 110 to 115 mmHg 11 .These cohort studies showed there was an increased risk of mortality at SBP levels outside this range 13,14 .The relative risk estimates for blood pressure outcomes have remained unchanged since GBD 2016.The results of the Renal Risk Collaboration meta-analysis, which included 2.7 million participants, were used to ascertain the relative risks related to chronic kidney disease 11 .The CALIBRE study, a cohort study that links health records in the United Kingdom, was used to model the relative risk (RR) for cardiovascular outcomes 14,15 .The estimates of relative risk for other outcomes were obtained from: the Asia Pacific Cohort Studies Collaboration (APCSC) and the Prospective Studies Collaboration (PSC) 16 .To analyze and aggregate effect sizes from the studies, DisMod-MR 2.1 was utilised to construct dose-response curves for each outcome related to HSBP 11 .This tool enabled the integration of random effects between studies and the inclusion of data covering diverse age categories.The IHME applied the relative risks consistently across every country, and meta-regression was used to combine data from the three major sources 11 .

Diseases associated with HSBP
The population-attributable fraction (PAF) was utilised to assess the impact of HSBP on disease and injury prevalence by nation, age category, sex, and year.To estimate the deaths and disability-adjusted life years (DALYs) due to HSBP, the PAFs were multiplied with the estimated death counts or DALYs in each country, specific disease or injury, age category, sex, and year 11 .
The mortality numbers were modelled using the Cause of Death Ensemble model (CODEm) within the Global Burden of Disease 2019 framework 10 .The CODEm algorithm employed multiple separate models to determine the most parsimonious fit, based on all available data and covariates.In addition, predictive validity was assessed for each model and combination of models.The model with the highest predictive validity, particularly in outof-sample circumstances, was selected.
The estimation of DALYs utilised a three-stage process.Firstly, the years lived with disability (YLDs) were estimated by multiplying the prevalence of each disease or injury severity category by their corresponding disability weights.Next, the calculation of years of life lost (YLLs) for each injury or disease was undertaken.The number of deaths in each age category were multiplied by the estimated number of years of life left, as obtained from the GBD standard life table, in each specific age category.Following this, the YLLs and YLDs were added together to estimate the total DALYs for each disease or injury 11 .The detailed methodology employed to estimate the overall number of deaths and DALYs has previously been published 10,11 .The estimates reported included counts, PAFs, and age-standardised rates (per 100,000), as well as 95% uncertainty intervals (UIs).The 95% UIs were produced by undertaking one thousand draws at each step in the modelling process and consisted of the 25th and 975th values of the numerically ordered iterations 11 .
In order to explore the association between the age-standardised DALY rate of HSBP-related diseases and the Socio-demographic Index (SDI) for all MENA countries, smoothing splines models were used 17 .As an indicator of socio-economic development, SDI ranges from the highest development level 1 to the lowest development level (0).SDI is constructed by combining the per capita income, educational attainment (≥ 15 years old) and overall fertility rate (< 25 years old).All figures and analyses were carried out with R software (version 3.5.2).

Individual country level
The proportion of deaths attributed to HSBP in 2019 ranged from 14.3% to 35%.The three countries with the highest PAFs were Morocco (  S3). Figure 1B displays the change in the age-standardised mortality rates for males and females from 1990 to 2019.1). Figure S2 shows the percentage changes in the age-standardised DALY rates for both sexes between 1990 and 2019.

Sex and age patterns
In 2019, the HSBP-related mortality and DALY rates rose with age for both sexes.Moreover, no significant sex differences in the HSBP-related death and DALY rates were observed in any age category (Fig. 2A and B).
In 2019, the HSBP-related death cases rose with age in both sexes, with the highest number of cases identified in individuals aged 75-79 years.Moreover, males had more HSBP-related death cases than females in those aged 40-59 years old (Fig. 2A).Furthermore, for both sexes the HSBP-related DALYs increased with age up to those aged 60-64, and then declined with advancing age.In addition, HSBP-related DALYs were higher among males in those aged 50-59 years old (Fig. 2B).

Underlying causes
In 2019, individuals aged 25 and above had the highest number of HSBP-attributable deaths and death rate from ischemic heart disease, stroke, and hypertensive heart.Notably, the number of fatalities and mortality rate due to stroke exceeded those caused by hypertensive heart disease for those aged 85-89 years old.In addition, the death rates from all HSBP-related diseases increased with age (Fig. 3A).This pattern was also found in the DALYs and the DALY rate from all diseases caused by HSBP in 2019 (Fig. 3B).

Relationship with Socio-Demographic Index (SDI)
In the period 1990-2019, SDI had a negative linear relationship with the age-standardised DALY rates attributed to HSBP.Those nations that were above the solid black line exceeded the expected burden, while a lower than expected burden was exhibited for the nations underneath the line.The age-standardised DALY rates shrank for the majority of countries between 1990 and 2019.Throughout the measuring period, burdens were higher than anticipated in Afghanistan, Egypt, Morocco, Oman, Sudan, the Syrian Arab Republic, and Iraq, while burdens were lower than anticipated in Iran, Kuwait, Lebanon, Libya, Palestine, Tunisia, Turkey, and Yemen (Fig. 4).

Discussion
This study utilized the methodological framework and data drawn from the GBD study 2019 to examine the HSBP-attributable burden in MENA from 1990 to 2019.The results shed light on the significant impact that HSBP has on the mortality and DALYs in the region.In 2019, it was estimated that HSBP was responsible for approximately 803.6 thousand deaths in the MENA region, and made up 25.9% of all deaths in MENA.Moreover, the total number of DALYs caused by HSBP in 2019 was 19.0 million, accounting for 11.6% of all DALYs.
There was a decline of 23.4% in the DALYs attributable to HSBP from 1990 to 2019, indicating some progress in addressing this health issue.Our findings further emphasize the impact of HSBP on cardiovascular health in the MENA region, particularly with regards to ischemic heart disease, hypertensive heart disease, and stroke.Furthermore, an inverse relationship was identified between the age-standardised DALY rates due to HSBP and the SDI.This implies that nations with higher development levels and better access to healthcare resources tend to have a lower disease burdens from HSBP 3 .Awareness, treatment, and control of HSBP are lower in nations that have lower SDIs than they are in nations with higher SDIs 18 .Low and middle SDI regions have increasing HSBP-related burdens, primarily because of limited awareness and fewer resources available for preventing, screening, and intervening 19,20 .Lifestyle factors can also play roles in the differences between countries in terms of the association between SDI and HSBPattributable burden.In this regard, the burden of diseases attributable to low physical activity increased with SDI up to about high-middle SDI, while it decreased in high SDI countries 21 .Moreover, evaluating the burden of cardiovascular diseases attributable to salt intake showed that middle-SDI countries had the highest values in 2019 compared with other SDI quintiles 22 .Although there are well-known evidence-based interventions for HSBP, and its related diseases, their implementation in low to middle income countries faces several challenges at the population level 19,23,24 .These challenges include cost considerations, limited financial resources, a lack of health insurance and facilities, infrequent interactions with healthcare providers, and the unavailability of some medicines 19 .Furthermore, expanding the coverage of treatment and enhancing its community-level impact can significantly alleviate the health burden associated with HSBP 19,23 .Effectively managing HSBP requires a holistic approach, encompassing both population level awareness campaigns and individual lifestyle modifications, particularly in resource constrained regions 25 .Consistent and affordable healthcare services can improve hypertension awareness, prevention, treatment, control, and compliance.However, additional research is required to evaluate the efficacy of these methods, identify which populations and situations they are most effective in, and to assess their impact on inequality, as some people may not have access to healthcare services that are available to those with higher incomes and education.
Our findings showed that over the last three decades, the burden of diseases attributable to HSBP significantly decreased in the MENA region.It might be explained by multiple factors influence the occurrence of hypertension in this area, including high levels of smoking, obesity, sedentary habits, certain gender disparities, and an inadequate healthcare infrastructure.Additionally, socio-economic elements and discrepancies in education, literacy, and urban development exert a considerable impact 26 .To maintain or enhance the trend, other initiatives Figure 4. Age-standardised DALY rates of diseases and injuries attributable high systolic blood pressure for the 21 Middle East and North Africa (MENA) countries by Socio-demographic Index, 2019; the black line shows the expected values, based upon the Socio-demographic Index and disease rates.Data points above the solid black line showed a higher-than-expected burden, while those below the line showed a lower than expected burden (both based on SDI).DALY = disability-adjusted life years.such as enhancing the accessibility and affordability of fresh fruits/vegetables, reducing the sodium levels in processed foods and common staples like bread, and enhancing the availability of salt alternatives in diets can be considered across the entire population 25 .Moreover, the adherence of patients to treatment emerges as a crucial aspect for controlling blood pressure and should be resolved 26 .
The link between hypertension and sodium intake is well-established and supported by multiple studies [27][28][29][30] .By reducing dietary sodium intake, individuals can decrease their blood pressure and risk of hypertension, in addition to reducing their chances of developing cardiovascular diseases and related health complications 27,28,31 .A systematic review and meta-analysis of 113 studies discovered that reducing dietary sodium intake led to a notable decrease in systolic blood pressure in adults 32 .In addition, reducing tobacco use, another substantial risk factor for cardiovascular diseases, is crucial for improving hypertension control and preventing cardiovascular diseases 33,34 .Therefore, a comprehensive strategy involving multiple components can be implemented to prevent, treat, and control hypertension in MENA.
Analysing the age-specific DALY rates revealed a common trend in both men and women, with rates progressively rising in younger age groups and reaching their peak among those aged 95 years and older.This suggests that HSBP has a cumulative effect over time, leading to a higher disease burden in older age groups.Men face higher exposure to social and environmental risk factors, including smoking tobacco, alcohol consumption, and unhealthy dietary habits 35 .Furthermore, they exhibit lower levels of awareness about hypertension and receive antihypertensive treatment less often than females 36 .These results underscore the need for specialised interventions and healthcare services that are tailored to the unique needs of different population subgroups.
While there have been no prior studies specifically addressing the HSBP burden in the MENA region, a number of global and country-specific studies have been published.Chen et al. used GBD 2019 to reported the all cause-specific burden that was due to HSBP 3 .They found a significant reduction in the global burden of HSBP-associated mortality from 1990 to 2019 3 .They also found that the burden linked to HSBP exhibited substantial regional, age, and sex variations 3 .Additionally, they also showed that in 2019, the HSBP-related burden was more pronounced in low and low-middle SDI regions, in comparison to regions with higher SDIs 3 .Furthermore, the age-standardised mortality rates for stroke and ischemic heart disease were also higher in areas with middle level SDIs, such as the Middle East 3 .However, they did not provide detailed estimates for the individual MENA countries.
Our findings have substantial implications for public health policy and planning in this region.They underscore the importance of early detection, prevention and management of hypertension, especially in individuals aged 25 and older, given the elevated mortality rates from ischemic heart disease associated with high systolic blood pressure.The high burden of HSBP necessitates a comprehensive and multifaceted approach to tackle this public health challenge.Efforts should promote regular blood pressure screening, lifestyle modifications, and effective pharmacological interventions to decrease blood pressure and to lower the likelihood of cardiovascular events [37][38][39] .Strategies should emphasize lifestyle modifications, including the promotion of smoking cessation, regularly engaging in physical exercise and maintaining a healthy diet [37][38][39] .Healthcare systems should be strengthened to ensure the timely diagnosis, effective treatment, and continuous management of HSBP 40 , with a particular focus on vulnerable populations and older people.Policies should address the social determinants of health, aiming to reduce inequalities and to improve access to healthcare services 41,42 .Early screening for hypertension can help identify it earlier and to reduce hypertension related health issues 43 , even though further research is required to examine the effectiveness of these strategies and to improve the accuracy of the screening methods 44,45 .This highlights the need for comprehensive cardiovascular health programs that address stroke prevention and the specific challenges associated with hypertensive heart disease in older age groups 2,46,47 .

Strengths and limitations
This research offers valuable insights into the burden of diseases associated with HSBP in MENA, but there are also several limitations that need to be acknowledged.Firstly, the performance of the model used to estimate the data produce wide UIs for some countries, which was primarily due to the limited availability of data.Nonetheless, our main objective was to report the most accurate estimations possible by utilising data from countries with a high degree of similarity.As a result, the national results provided here should be interpreted with caution, particularly for Afghanistan, Sudan, and Yemen, due to the devastation caused by war and civil instability.Secondly, the study solely focused on the burden attributable to HSBP and did not explore other risk factors or comorbidities that may have contributed to the burden of cardiovascular diseases in MENA.Future research is required to comprehensively assess the impact of cardiovascular diseases and their related risk factors.Thirdly, the analysis was based on data from 1990 to 2019, although more recent data may provide additional insights into the changing HSBP burden in MENA.Fourthly, the GBD project only reported the burden of diseases attributable to HSBP, so we did not have the data to evaluate the burden of diseases attributable to high diastolic blood pressure.We also acknowledge the previously described methodological shortcomings of the GBD 2019 study 10,11 .

Conclusions
The MENA region has a substantial burden of diseases attributable to HSBP.The findings underscore the need for comprehensive efforts to prevent and manage HSBP, considering its significant impact on mortality and DALYs.The observed decline in the DALY rates attributable to HSBP indicates that there has been some progress in addressing this important public health issue, although the burden remains large.Policymakers and healthcare professionals should prioritise interventions that effectively promote the early detection of HSBP, access to quality healthcare, and lifestyle modifications to reduce the burden of HSBP.Addressing the risk factors and implementing evidence-based strategies can mitigate the adverse health outcomes associated with HSBP, which will lead to improvements in the overall health and well-being of those living in the MENA region.

Figure 1 .
Figure 1.Age-standardised death rate (per 100,000 population) in 2019 (A) and the percentage change in the age-standardised death rate from 1990 to 2019 (B) of diseases and injuries attributable to high systolic blood pressure in the Middle East and North Africa region, by sex and country.(Generated from data available from http:// ghdx.healt hdata.org/ gbd-resul ts-tool).

Figure
Figure Numbers of deaths and death rate (A) and number of DALYs and DALY rate (B) of diseases and injuries attributable to high systolic blood pressure in the Middle East and North Africa region, by age and sex in 2019 Dotted and dashed lines indicate 95% upper and lower uncertainty intervals, respectively.DALY = Disability-adjusted life-year.(Generated from data available from http:// ghdx.healt hdata.org/ gbd-resul ts-tool).

Figure 3 .
Figure 3. Numbers of deaths and death rate (A) and number of DALYs and DALY rate (B) of diseases and injuries attributable to high systolic blood pressure in the Middle East and North Africa region, by age and cause in 2019.DALY = Disability-adjusted life-year.(Generated from data available from http:// ghdx.healt hdata.org/ gbd-resul ts-tool).